Proteomic Profiles in Advanced Age-Related Macular Degeneration Using an Aptamer-Based Proteomic Technology

Abstract

Purpose: To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA.

Methods: We conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome.

Results: In this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor-related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling.

Conclusions: We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described.

Translational relevance: Biomarkers identified in plasma likely reflect systemic alterations in protein expression and may improve our understanding of the mechanisms leading to AMD.

Keywords: aptamer-based technologies; geographic atrophy; neovascular AMD; proteomics.

Figure 1

Differences between group means in cases of neovascular (NV) AMD compared with cataract controls, where a difference of 1 on log₂ scale corresponds to a fold change of two.

Figure 2

Differences between group means in cases of geographic atrophy (GA) compared with cataract controls, where a difference of 1 on log₂ scale corresponds to a fold change of two.

Figure 3

Distribution of select proteins in patients with GA, NV AMD, and cataract controls. The box indicates the interquartile range (IQR; 25th–75th percentile) and the median and mean are indicated by the lines and diamonds, respectively. Whiskers indicate data within 1.5 times the IQR, and points indicate individual data values.